rs2235040 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235040 is one of 9 SNPs found within a tight linkage block (r2 >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below.
When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are known to be substrates include citalopram, paroxetine, amitriptyline, and venlafaxine. The relative odds of better response for rs2235040(G) carriers is 7.72 (CI: 2.8-21.3, p=0.000065) based on a study of ~400 primarily Caucasian patients.10.1016/j.neuron.2007.11.017
The 9 SNPs in the linkage block identified are 10.1016/j.neuron.2007.11.017:
[PMID 18382661] Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.
[PMID 22641028] ABCB1 gene variants influence tolerance to selective serotonin reuptake inhibitors in a large sample of Dutch cases with major depressive disorder.
|qualified_impact||Insufficiently evaluated pharmacogenetic|